Evaluation of Glucosinolate Levels Throughout the Production Chain of Brassicavegetable S
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Report of the Advisory Group to Recommend Priorities for the IARC Monographs During 2020–2024
IARC Monographs on the Identification of Carcinogenic Hazards to Humans Report of the Advisory Group to Recommend Priorities for the IARC Monographs during 2020–2024 Report of the Advisory Group to Recommend Priorities for the IARC Monographs during 2020–2024 CONTENTS Introduction ................................................................................................................................... 1 Acetaldehyde (CAS No. 75-07-0) ................................................................................................. 3 Acrolein (CAS No. 107-02-8) ....................................................................................................... 4 Acrylamide (CAS No. 79-06-1) .................................................................................................... 5 Acrylonitrile (CAS No. 107-13-1) ................................................................................................ 6 Aflatoxins (CAS No. 1402-68-2) .................................................................................................. 8 Air pollutants and underlying mechanisms for breast cancer ....................................................... 9 Airborne gram-negative bacterial endotoxins ............................................................................. 10 Alachlor (chloroacetanilide herbicide) (CAS No. 15972-60-8) .................................................. 10 Aluminium (CAS No. 7429-90-5) .............................................................................................. 11 -
Bioavailability of Sulforaphane from Two Broccoli Sprout Beverages: Results of a Short-Term, Cross-Over Clinical Trial in Qidong, China
Cancer Prevention Research Article Research Bioavailability of Sulforaphane from Two Broccoli Sprout Beverages: Results of a Short-term, Cross-over Clinical Trial in Qidong, China Patricia A. Egner1, Jian Guo Chen2, Jin Bing Wang2, Yan Wu2, Yan Sun2, Jian Hua Lu2, Jian Zhu2, Yong Hui Zhang2, Yong Sheng Chen2, Marlin D. Friesen1, Lisa P. Jacobson3, Alvaro Muñoz3, Derek Ng3, Geng Sun Qian2, Yuan Rong Zhu2, Tao Yang Chen2, Nigel P. Botting4, Qingzhi Zhang4, Jed W. Fahey5, Paul Talalay5, John D Groopman1, and Thomas W. Kensler1,5,6 Abstract One of several challenges in design of clinical chemoprevention trials is the selection of the dose, formulation, and dose schedule of the intervention agent. Therefore, a cross-over clinical trial was undertaken to compare the bioavailability and tolerability of sulforaphane from two of broccoli sprout–derived beverages: one glucoraphanin-rich (GRR) and the other sulforaphane-rich (SFR). Sulfor- aphane was generated from glucoraphanin contained in GRR by gut microflora or formed by treatment of GRR with myrosinase from daikon (Raphanus sativus) sprouts to provide SFR. Fifty healthy, eligible participants were requested to refrain from crucifer consumption and randomized into two treatment arms. The study design was as follows: 5-day run-in period, 7-day administration of beverages, 5-day washout period, and 7-day administration of the opposite intervention. Isotope dilution mass spectrometry was used to measure levels of glucoraphanin, sulforaphane, and sulforaphane thiol conjugates in urine samples collected daily throughout the study. Bioavailability, as measured by urinary excretion of sulforaphane and its metabolites (in approximately 12-hour collections after dosing), was substantially greater with the SFR (mean ¼ 70%) than with GRR (mean ¼ 5%) beverages. -
Indole Carbinol: a Glucosinolate Derivative from Cruciferous
Research Indole-3-carbinol: A glucosinolate derivative from cruciferous vegetables for prevention and complementary treatment of breast cancer Ben L. Pfeifer1, Theodor Fahrendorf2 Summary spect seem to be secondary plant sub- stances from cruciferous vegetables, Breast cancer is the most common malignancy in women today. Despite such as indole 3-carbinol (I3C). This is a improved therapies, only every second woman with breast cancer can ex- glucosinolate derivative containing sul- pect cure. If cancer is metastatic at diagnosis, or recurs with metastases, phur whose metabolic products are then treatment is limited to palliative measures only, and cure is usually not widely known for their anti-cancer expected. Under these circumstances, quality of life as well as overall surviv- effects [34-36, 44, 46]. Detailed studies al of the patient is significantly reduced. It is therefore advisable for pa- have been carried out regarding their tients, their physicians, and the entire society at large, to search for more preventive and therapeutic effectiveness effective and less toxic treatment methods and develop better prevention in treating breast cancer and other types strategies that can reduce the burden of this cancer on the individual pa- tient and society as a whole. Indole-3-carbinol, a glucosinolate derivative of cancer [7, 12, 18, 30, 62, 79]. Labora- from cruciferous vegetables, seems to be a strong candidate to achieve tory tests on cell cultures and animal ex- these goals. It is abundantly available, well tolerated and non-toxic. Suffi- periments showed that I3C prevents the cient amounts for prevention of breast cancer can be taken up by daily con- development of cancer in various organs sumption of cruciferous vegetables. -
MINI-REVIEW Cruciferous Vegetables: Dietary Phytochemicals for Cancer Prevention
DOI:http://dx.doi.org/10.7314/APJCP.2013.14.3.1565 Glucosinolates from Cruciferous Vegetables for Cancer Chemoprevention MINI-REVIEW Cruciferous Vegetables: Dietary Phytochemicals for Cancer Prevention Ahmad Faizal Abdull Razis1*, Noramaliza Mohd Noor2 Abstract Relationships between diet and health have attracted attention for centuries; but links between diet and cancer have been a focus only in recent decades. The consumption of diet-containing carcinogens, including polycyclic aromatic hydrocarbons and heterocyclic amines is most closely correlated with increasing cancer risk. Epidemiological evidence strongly suggests that consumption of dietary phytochemicals found in vegetables and fruit can decrease cancer incidence. Among the various vegetables, broccoli and other cruciferous species appear most closely associated with reduced cancer risk in organs such as the colorectum, lung, prostate and breast. The protecting effects against cancer risk have been attributed, at least partly, due to their comparatively high amounts of glucosinolates, which differentiate them from other vegetables. Glucosinolates, a class of sulphur- containing glycosides, present at substantial amounts in cruciferous vegetables, and their breakdown products such as the isothiocyanates, are believed to be responsible for their health benefits. However, the underlying mechanisms responsible for the chemopreventive effect of these compounds are likely to be manifold, possibly concerning very complex interactions, and thus difficult to fully understand. Therefore, -
Anti-Carcinogenic Glucosinolates in Cruciferous Vegetables and Their Antagonistic Effects on Prevention of Cancers
molecules Review Anti-Carcinogenic Glucosinolates in Cruciferous Vegetables and Their Antagonistic Effects on Prevention of Cancers Prabhakaran Soundararajan and Jung Sun Kim * Genomics Division, Department of Agricultural Bio-Resources, National Institute of Agricultural Sciences, Rural Development Administration, Wansan-gu, Jeonju 54874, Korea; [email protected] * Correspondence: [email protected] Academic Editor: Gautam Sethi Received: 15 October 2018; Accepted: 13 November 2018; Published: 15 November 2018 Abstract: Glucosinolates (GSL) are naturally occurring β-D-thioglucosides found across the cruciferous vegetables. Core structure formation and side-chain modifications lead to the synthesis of more than 200 types of GSLs in Brassicaceae. Isothiocyanates (ITCs) are chemoprotectives produced as the hydrolyzed product of GSLs by enzyme myrosinase. Benzyl isothiocyanate (BITC), phenethyl isothiocyanate (PEITC) and sulforaphane ([1-isothioyanato-4-(methyl-sulfinyl) butane], SFN) are potential ITCs with efficient therapeutic properties. Beneficial role of BITC, PEITC and SFN was widely studied against various cancers such as breast, brain, blood, bone, colon, gastric, liver, lung, oral, pancreatic, prostate and so forth. Nuclear factor-erythroid 2-related factor-2 (Nrf2) is a key transcription factor limits the tumor progression. Induction of ARE (antioxidant responsive element) and ROS (reactive oxygen species) mediated pathway by Nrf2 controls the activity of nuclear factor-kappaB (NF-κB). NF-κB has a double edged role in the immune system. NF-κB induced during inflammatory is essential for an acute immune process. Meanwhile, hyper activation of NF-κB transcription factors was witnessed in the tumor cells. Antagonistic activity of BITC, PEITC and SFN against cancer was related with the direct/indirect interaction with Nrf2 and NF-κB protein. -
Synthesis of Isothiocyanates Using DMT/NMM/Tso− As a New Desulfurization Reagent
molecules Article Synthesis of Isothiocyanates Using DMT/NMM/TsO− as a New Desulfurization Reagent Łukasz Janczewski 1,* , Dorota Kr˛egiel 2 and Beata Kolesi ´nska 1 1 Faculty of Chemistry, Institute of Organic Chemistry, Lodz University of Technology, Zeromskiego 116, 90-924 Lodz, Poland; [email protected] 2 Department of Environmental Biotechnology, Faculty of Biotechnology and Food Sciences, Lodz University of Technology, Wolczanska 171/173, 90-924 Lodz, Poland; [email protected] * Correspondence: [email protected] Abstract: Thirty-three alkyl and aryl isothiocyanates, as well as isothiocyanate derivatives from esters of coded amino acids and from esters of unnatural amino acids (6-aminocaproic, 4-(aminomethyl)benzoic, and tranexamic acids), were synthesized with satisfactory or very good yields (25–97%). Synthesis was performed in a “one-pot”, two-step procedure, in the presence of organic base (Et3N, DBU or NMM), and carbon disulfide via dithiocarbamates, with 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4- methylmorpholinium toluene-4-sulfonate (DMT/NMM/TsO−) as a desulfurization reagent. For the synthesis of aliphatic and aromatic isothiocyanates, reactions were carried out in a microwave reactor, and selected alkyl isothiocyanates were also synthesized in aqueous medium with high yields (72–96%). Isothiocyanate derivatives of L- and D-amino acid methyl esters were synthesized, under conditions without microwave radiation assistance, with low racemization (er 99 > 1), and their absolute configuration was confirmed by circular dichroism. Isothiocyanate derivatives of natural and unnatural amino acids were evaluated for antibacterial activity on E. coli and S. aureus bacterial strains, where the Citation: Janczewski, Ł.; Kr˛egiel,D.; most active was ITC 9e. -
Figure 1. Metabolism of Glucoraphanin and Glucobrassicin to Biologically Active Metabolites
Legend to Figures: Figure 1. Metabolism of glucoraphanin and glucobrassicin to biologically active metabolites. (A) Sulforaphane is released from glucoraphanin by the plant enzyme myrosinase. Red dashed arrow marks the reactive carbon atom subject to glutathione conjugation. (B) Sulforaphane is metabolized via the mercapturic acid pathway into active metabolites. Glutathione-S-transferase (GST) first conjugates a GSH molecule (Glu-Cys-Gly) to the reactive carbon on sulforaphane. Glutamate is then removed by γ- glutamyltranspeptidase (GTP), followed by removal of the glycine residue by cysteinylglycinase (CGase). Cysteine is then acetylated by an acetyltransferase (AT) to sulforaphane-N-acetylcysteine, which is excreted in the urine. (C) Indole-3-carbinol is released from the glucosinolate glucobrassicin by myrosinase and undergoes spontaneous condensation in the acidic environment of the gut. Diindolylmethane (DIM) is the most abundant post-absorption acid condensation product. Acid condensation products can be modified further post-absorption. LTr1: Linear trimer 1. LTr2: Linear trimer 2. Structures from PubChem at National Center for Biotechnology Information (NCBI). Figure 2. Selected non-epigenetic effects of sulforaphane and I3C/DIM on prostate cancer cells. Sulforaphane (SFN) and I3C/DIM inhibit the Akt signaling axis, a signaling pathway often hyperactive in prostate cancer. Inhibition of this pathway decreases pro-survival signaling by mTOR, Akt, and NFkB. Sulforaphane and I3C/DIM treatment also lead to changes in gene expression (blue arrow) that trigger growth arrest and apoptosis. The expression of proteins controlling the cell cycle (e.g. p21, p27, CDK6) are altered to effect growth arrest, and apoptosis is finally induced through the mitochondrial pathway. Abbreviations: AR – Androgen Receptor, CDK6 – cyclin dependant kinase 6, IAP – inhibitors of apoptosis. -
Effects of Cruciferous Vegetable Consumption on Urinary
Cancer Epidemiology, Biomarkers & Prevention 997 Effects of Cruciferous Vegetable Consumption on Urinary Metabolites of the Tobacco-Specific Lung Carcinogen 4-(Methylnitrosamino)-1-(3-Pyridyl)-1-Butanone in Singapore Chinese Stephen S. Hecht,1 Steven G. Carmella,1 Patrick M.J. Kenney,1 Siew-Hong Low,2 Kazuko Arakawa,3 and Mimi C. Yu3 1University of Minnesota Cancer Center, Minneapolis, Minnesota; 2Department of Community, Occupational, and Family Medicine, National University of Singapore, Singapore; and 3Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, California Abstract Vegetable consumption, including cruciferous vegeta- major glucosinolates in seven of the nine cruciferous bles, is protective against lung cancer, but the mechan- vegetables, accounting for 70.0% to 93.2% of all glu- isms are poorly understood. The purpose of this study cosinolates in these vegetables. There was a significant was to investigate the effects of cruciferous vegetable correlation (P = 0.01) between increased consumption consumption on the metabolism of the tobacco-specific of glucobrassicins and decreased levels of NNAL in lung carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1- urine after adjustment for number of cigarettes smoked butanone (NNK) in smokers. The study was carried out per day; similar trends were observed for NNAL-Glucs in Singapore Chinese, whose mean daily intake of (P = 0.08) and NNAL plus NNAL-Glucs (P = 0.03). cruciferous vegetables is three times greater than that These results are consistent with those of previous of people in the United States. Eighty-four smokers studies, which demonstrate that indole-3-carbinol de- provided urine samples and were interviewed about creases levels of urinary NNAL probably by inducing dietary habits using a structured questionnaire, which hepatic metabolism of NNK. -
WO 2014/149829 Al 25 September 2014 (25.09.2014) P O P C T
(12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization International Bureau (10) International Publication Number (43) International Publication Date WO 2014/149829 Al 25 September 2014 (25.09.2014) P O P C T (51) International Patent Classification: KZ, LA, LC, LK, LR, LS, LT, LU, LY, MA, MD, ME, A23L 1/22 (2006.01) MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, PA, PE, PG, PH, PL, PT, QA, RO, RS, RU, RW, SA, (21) International Application Number: SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, PCT/US2014/021 110 TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, (22) International Filing Date: ZW. 6 March 2014 (06.03.2014) (84) Designated States (unless otherwise indicated, for every (25) Filing Language: English kind of regional protection available): ARIPO (BW, GH, GM, KE, LR, LS, MW, MZ, NA, RW, SD, SL, SZ, TZ, (26) Publication Language: English UG, ZM, ZW), Eurasian (AM, AZ, BY, KG, KZ, RU, TJ, (30) Priority Data: TM), European (AL, AT, BE, BG, CH, CY, CZ, DE, DK, 61/788,528 15 March 2013 (15.03.2013) US EE, ES, FI, FR, GB, GR, HR, HU, IE, IS, IT, LT, LU, LV, 61/945,500 27 February 2014 (27.02.2014) US MC, MK, MT, NL, NO, PL, PT, RO, RS, SE, SI, SK, SM, TR), OAPI (BF, BJ, CF, CG, CI, CM, GA, GN, GQ, GW, (71) Applicant: AFB INTERNATIONAL [US/US]; 3 Re KM, ML, MR, NE, SN, TD, TG). -
Anthocyanin and Glucosinolate Nutrients
ANTHOCYANIN AND GLUCOSINOLATE NUTRIENTS: AN EXPLORATION OF THE MOLECULAR BASIS AND IMPACT OF COLORFUL PHYTOCHEMICALS ON HUMAN HEALTH Abstract: Can eating food of an assortment of colors help one stay healthy? In this study, a randomized con- trolled trial helped evaluate the impact of a colorful diet on 8 healthy human adults (age 20-60) with similar demographic and dietary backgrounds. One of the daily meals of the volunteers was substituted with a hand- picked ration consisting of all colors of the rainbow in the form of a Rainbow Diet Pack (RDP). Fruits and vegeta- bles were chosen based on the exclusive molecular structure and chemical composition of the most prevalent phytonutrient(s) in each. RDP was administered daily to the intervention group (n=5) over a 10-wk interven- tion period. Weight loss, waist circumference, hand grip strength, and stress levels were measured. Analyses re- vealed that eating raspberries, oranges, carrots, broccoli, blueberries, and bananas balanced stress levels and led to weight loss, but did not impact hand-grip strength, demonstrating the healthy outcomes of a colorful diet.. BY AKSHARA SREE CHALLA1 AND JNANA ADITYA CHALLA2 LAYOUT OUT BY ANNALISE KAMEGAWA, EDNA STEWART, CAMERON MANDLEY, JENNY KIM INTRODUCTION precursors.7 Anthocyanins are also found in raspberries, which Te idea that one should be eating healthy to stay healthy is not are high in dietary fber and vitamin C and have a low glycemic a debate. Numerous studies show how particular foods indi- index because they contain 6% fber and only 4% sugar per total vidualistically efect human health, but none thus far, to our weight.8 Higher quantities of fber in the fruit, when consumed, knowledge, have investigated about the combined impact of a helps lower the levels of low-density lipoprotein (LDL) or the specifc diet on the human body as a whole.1-5 It is critical for us ‘unhealthy’ cholesterol to enhance the functionality of our heart to understand which kinds of things we should eat and the ways and potentially induce weight loss. -
Broccoli Or Sulforaphane: Is It the Source Or Dose That Matters?
molecules Review Broccoli or Sulforaphane: Is It the Source or Dose That Matters? Yoko Yagishita 1, Jed W. Fahey 2,3,4, Albena T. Dinkova-Kostova 3,4,5 and Thomas W. Kensler 1,4,* 1 Translational Research Program, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA; [email protected] 2 Department of Medicine, Division of Clinical Pharmacology, Johns Hopkins School of Medicine, Baltimore, MD 21205, USA; [email protected] 3 Department of Pharmacology and Molecular Sciences, Johns Hopkins School of Medicine, Baltimore, MD 21205, USA 4 Cullman Chemoprotection Center, Johns Hopkins School of Medicine, Baltimore, MD 21205, USA 5 Jacqui Wood Cancer Centre, Division of Cellular Medicine, Ninewells Hospital and Medical School, University of Dundee, Dundee DD1 9SY, Scotland DD1 9SY, UK; [email protected] * Correspondence: [email protected]; Tel.: +1-206-667-6005 Academic Editor: Gary D. Stoner Received: 24 September 2019; Accepted: 2 October 2019; Published: 6 October 2019 Abstract: There is robust epidemiological evidence for the beneficial effects of broccoli consumption on health, many of them clearly mediated by the isothiocyanate sulforaphane. Present in the plant as its precursor, glucoraphanin, sulforaphane is formed through the actions of myrosinase, a β-thioglucosidase present in either the plant tissue or the mammalian microbiome. Since first isolated from broccoli and demonstrated to have cancer chemoprotective properties in rats in the early 1990s, over 3000 publications have described its efficacy in rodent disease models, underlying mechanisms of action or, to date, over 50 clinical trials examining pharmacokinetics, pharmacodynamics and disease mitigation. This review evaluates the current state of knowledge regarding the relationships between formulation (e.g., plants, sprouts, beverages, supplements), bioavailability and efficacy, and the doses of glucoraphanin and/or sulforaphane that have been used in pre-clinical and clinical studies. -
Broccoli Sprout Beverage Is Safe for Thyroid Hormonal and Autoimmune Status: Results of a 12-Week Randomized Trial T
Food and Chemical Toxicology 126 (2019) 1–6 Contents lists available at ScienceDirect Food and Chemical Toxicology journal homepage: www.elsevier.com/locate/foodchemtox Broccoli sprout beverage is safe for thyroid hormonal and autoimmune status: Results of a 12-week randomized trial T Dionysios V. Chartoumpekisa,2, Panos G. Zirosb, Jian-Guo Chenc, John D. Groopmand, ∗ Thomas W. Kenslera,1,3, Gerasimos P. Sykiotisb, ,1 a Department of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, PA, 15261, USA b Service of Endocrinology, Diabetology and Metabolism, Lausanne University Hospital, Lausanne, Switzerland c Department of Epidemiology, Qidong Liver Cancer Institute, Qidong, Jiangsu, China d Department of Environmental Health and Engineering, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, 21205, USA ARTICLE INFO ABSTRACT Keywords: Sulforaphane is a redox-active natural product present in cruciferous vegetables like broccoli. Broccoli sprout- Nrf2 derived products are promising agents for the prevention of oxidative stress-related diseases, but some have long Thyroid been suspected of thyroidal toxicity. Recent findings also raise the possibility that long-term exposure to sul- Sulforaphane foraphane, or to other natural substances or drugs that modulate the activity of the transcription factor Nrf2 Glucoraphanin (NFE2-related factor 2) may lead to thyroid dysfunction or thyroid autoimmune disease, questioning the safety Broccoli sprout beverage of trials with sulforaphane-containing products. Previous studies addressing possible effects of sulforaphane- Clinical trial related compounds from natural product extracts on the thyroid were quite short and/or inconsistent. To in- vestigate whether long-term exposure to a beverage enriched with sulforaphane and its precursor glucoraphanin may affect thyroid function, we analyzed biochemical measures of thyroid function and thyroid autoimmunity in 45 female participants in a randomized clinical trial at baseline and after 84 days of beverage administration.